HAND2 Target Gene Regulatory Networks Control Atrioventricular Canal and Cardiac Valve Development
Abstract
The HAND2 transcriptional regulator controls cardiac development, and we uncover additional essential functions in the endothelial to mesenchymal transition (EMT) underlying cardiac cushion development in the atrioventricular canal (AVC). In Hand2-deficient mouse embryos, the EMT underlying AVC cardiac cushion formation is disrupted, and we combined ChIP-seq of embryonic hearts with transcriptome analysis of wild-type and mutants AVCs to identify the functionally relevant HAND2 target genes. The HAND2 target gene regulatory network (GRN) includes most genes with known functions in EMT processes and AVC cardiac cushion formation. One of these is Snai1, an EMT master regulator whose expression is lost from Hand2-deficient AVCs. Re-expression of Snai1 in mutant AVC explants partially restores this EMT and mesenchymal cell migration. Furthermore, the HAND2-interacting enhancers in the Snai1 genomic landscape are active in embryonic hearts and other Snai1-expressing tissues. These results show that HAND2 directly regulates the molecular cascades initiating AVC cardiac valve development.
- Authors:
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE; National Institutes of Health (NIH)
- OSTI Identifier:
- 1619828
- Alternate Identifier(s):
- OSTI ID: 1379857
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Published Article
- Journal Name:
- Cell Reports
- Additional Journal Information:
- Journal Name: Cell Reports Journal Volume: 19 Journal Issue: 8; Journal ID: ISSN 2211-1247
- Publisher:
- Elsevier
- Country of Publication:
- Netherlands
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES
Citation Formats
Laurent, Frédéric, Girdziusaite, Ausra, Gamart, Julie, Barozzi, Iros, Osterwalder, Marco, Akiyama, Jennifer A., Lincoln, Joy, Lopez-Rios, Javier, Visel, Axel, Zuniga, Aimée, and Zeller, Rolf. HAND2 Target Gene Regulatory Networks Control Atrioventricular Canal and Cardiac Valve Development. Netherlands: N. p., 2017.
Web. doi:10.1016/j.celrep.2017.05.004.
Laurent, Frédéric, Girdziusaite, Ausra, Gamart, Julie, Barozzi, Iros, Osterwalder, Marco, Akiyama, Jennifer A., Lincoln, Joy, Lopez-Rios, Javier, Visel, Axel, Zuniga, Aimée, & Zeller, Rolf. HAND2 Target Gene Regulatory Networks Control Atrioventricular Canal and Cardiac Valve Development. Netherlands. https://doi.org/10.1016/j.celrep.2017.05.004
Laurent, Frédéric, Girdziusaite, Ausra, Gamart, Julie, Barozzi, Iros, Osterwalder, Marco, Akiyama, Jennifer A., Lincoln, Joy, Lopez-Rios, Javier, Visel, Axel, Zuniga, Aimée, and Zeller, Rolf. Mon .
"HAND2 Target Gene Regulatory Networks Control Atrioventricular Canal and Cardiac Valve Development". Netherlands. https://doi.org/10.1016/j.celrep.2017.05.004.
@article{osti_1619828,
title = {HAND2 Target Gene Regulatory Networks Control Atrioventricular Canal and Cardiac Valve Development},
author = {Laurent, Frédéric and Girdziusaite, Ausra and Gamart, Julie and Barozzi, Iros and Osterwalder, Marco and Akiyama, Jennifer A. and Lincoln, Joy and Lopez-Rios, Javier and Visel, Axel and Zuniga, Aimée and Zeller, Rolf},
abstractNote = {The HAND2 transcriptional regulator controls cardiac development, and we uncover additional essential functions in the endothelial to mesenchymal transition (EMT) underlying cardiac cushion development in the atrioventricular canal (AVC). In Hand2-deficient mouse embryos, the EMT underlying AVC cardiac cushion formation is disrupted, and we combined ChIP-seq of embryonic hearts with transcriptome analysis of wild-type and mutants AVCs to identify the functionally relevant HAND2 target genes. The HAND2 target gene regulatory network (GRN) includes most genes with known functions in EMT processes and AVC cardiac cushion formation. One of these is Snai1, an EMT master regulator whose expression is lost from Hand2-deficient AVCs. Re-expression of Snai1 in mutant AVC explants partially restores this EMT and mesenchymal cell migration. Furthermore, the HAND2-interacting enhancers in the Snai1 genomic landscape are active in embryonic hearts and other Snai1-expressing tissues. These results show that HAND2 directly regulates the molecular cascades initiating AVC cardiac valve development.},
doi = {10.1016/j.celrep.2017.05.004},
journal = {Cell Reports},
number = 8,
volume = 19,
place = {Netherlands},
year = {Mon May 01 00:00:00 EDT 2017},
month = {Mon May 01 00:00:00 EDT 2017}
}
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https://doi.org/10.1016/j.celrep.2017.05.004
https://doi.org/10.1016/j.celrep.2017.05.004
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Works referencing / citing this record:
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